p21.sup.WAF1 is a protein that may be transcriptionally induced by the tumour suppression protein p53 and acts as a potent inhibitor of cyclin dependent kinases (Cdks) in G1 and S phases of the cell cycle. Thus, p21.sup.WAF1 acts as a regulator of the cell cycle in response to activation of the p53 checkpoint pathway at least in part by inhibiting Cdk activity (1-3). p21.sup.WAf1 is also known as p21.sup.CIP1 (9) p21.sup.pic (33) p20.sup.CAP (34) and Sdi1 (35).
Complexes between p21.sup.WAF1 and Cdks can exist in both catalytically active and inactive forms, suggesting that the regulation is a subtle effect (4). p21.sup.WAF1 has also been reported to bind to PCNA at high concentration in vitro and block DNA replication (5). PCNA is a processivity factor for polymerase .delta. which plays an essential role in DNA replication and repair (6, 7). In transformed cell lines, p21.sup.WAF1 expression is depressed, and cyclin dependent kinases are found in a Cdk/cyclin binary state, rather than in Cdk/Cyclin/p21.sup.WAF1 /PCNA complexes, although the stoichiometry of these complexes is not clear (1, 8-10). Thus, it appears that during p53-mediated suppression of cell proliferation, p21.sup.WAF1 is important for co-ordinating cell cycle progression, DNA replication and repair of damaged DNA.